The somatic cell genetics of the instability of immunoglobulin genes in cultured hybridoma and myeloma cells will be studied. Earlier studies had shown that mutants with changes in the variable and constant regions of immunoglobulins arise frequently and spontaneously in cultured cells. The molecular and genetic mechanisms of these events will be examined by determining the relative rates of V and C region mutations and the base changes that occur in these mutants. Similar mutants will be sought in vivo. Mutants with both increases and decreases in antigen binding and changes in effector functions will be identified. The structural basis of these changes will be determined and the information gained will be used to construct antibodies that could be more effective reagents in protection against infection, neutralization of toxins, and targeting to tumors. (HI)